A model for the generation of persistent infection will be established. Chickens chronically infected with avian reovirus sometimes develop an arthritis closely resembling human rheumatoid arthritis. The studies proposed will examine the early viral events occurring during persistent infection of reoviruses in chickens and the components of the host immune response which are elicited. Previous investigations have suggested that two genes, S2, and S4, and possibly a third S1, are associated with persistence and S1 has also been implicated in viral virulence. Proposed studies will attempt to separate and evaluate the role of each gene in persistence. As the viral genome is segmented, reassortant viruses having gene combinations of interest will be developed for use in these studies. Attempts will be made 1) to reconfirm the association of S2, S4, and S1 with persistence in vivo by biochemical analysis of isolates obtained from individual chickens during the course of persistent infection and by evaluation of the ability of selected reassortants to become persistent; 2) to examine the patterns of protein and RNA synthesis of these strains in vitro to determine the functions of the proteins coded for by these genes and to investigate by tryptic peptide analysis the relationship of function to structure; and 3) to see if a correlation exists between in vitro and in vivo infections determining the arthrogenicity of the virus by Northern blotting, Western blotting and Elisa. The information gained will characterize the evolution of the virus during persistence.